CD28
生物
磷脂酰肌醇
T细胞
细胞因子
酪氨酸磷酸化
细胞生物学
克隆无能
信号转导
磷酸化
分子生物学
T细胞受体
免疫学
免疫系统
作者
Andrea Joss,Mübeccel Akdiş,A. Faith,Kurt Blaser,Cezmi A. Akdiş
标识
DOI:10.1002/1521-4141(200006)30:6<1683::aid-immu1683>3.0.co;2-a
摘要
IL-10 induces T cell anergy in numerous mouse models and specific immunotherapy of allergy in humans. Here, we demonstrate that IL-10 directly acts on T cells which are stimulated via CD28 by efficiently blocking proliferation and cytokine production. T cells tolerized by IL-10 showed high viability and the unresponsive state was reversed by anti-CD3 monoclonal antibody (mAb) stimulation and IL-2, but not by anti-CD28 mAb stimulation. Signal transduction via CD28 requires CD28 tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase. IL-10 inhibited tyrosine phosphorylation of CD28; thus, the phosphatidylinositol 3-kinase binding to CD28 was blocked. Consequently, IL-10 inhibited the antigen-induced secretion of both Th1 and Th2 cytokines, including IL-2, IFN-gamma, IL-4, IL-5 and IL-13. Furthermore, neutralization of endogenously produced IL-10 significantly increased T cell proliferation and both Th1 and Th2 cytokine production in vitro. Using superantigen stimuli, T cell suppression by IL-10 was merely induced at low doses when co-stimulation by CD28 was essential. Together, these data demonstrate that IL-10 directly acts on the CD28 signaling pathway and this represents an important T cell suppression mechanism leading to anergy.
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